This application will characterize the development and longitudinal progression of cardiovascular disease (CVD) risk factors in relation to biochemical markers of obesity metabolism in a multi-ethnic population of women, considering the 10-year period of the menopausal transition. In the process, the study will provide unique and needed information to address the public health obesity crisis at the age threshold for expression of chronic diseases of the elderly. This study will be conducted using existing data and Repository specimen resources of SWAN (Study of Women's Health Across the Nation), a prospective, multi-ethnic, multi-site evaluation of the menopausal transition in 3,302 women (aged 42-52 years at the 1996/97 baseline). The specific aims are 1) to characterize the cross-sectional and longitudinal relationships between obesity-related metabolites and CVD risk markers, including the clustering of CVD risk markers; 2) to determine the relative contributions of chronological and ovarian aging (e.g., menopause stages and reproductive hormones) to obesity-related markers levels and their changes (ghrelin and the adipocytokines adiponectin, resistin, and leptin); and 3) characterize if and when measures of ovarian aging modify relationships between obesity markers and CVD risk markers. Thus, this will be the first examination of the interrelationships between biochemical markers of obesity metabolism, ovarian aging, and CVD risk. These proposed aims will be addressed using existing SWAN data and SWAN Repository specimens from 1) all women present at the 6th annual SWAN follow-up visit (for cross-sectional analyses), and 2) all women who have experienced their final menstrual period and have specimen and covariate data within each of the 4 phases of the menopausal transition (for longitudinal analyses). Much remains unknown regarding the mechanisms which underlie the CVD risk associated with obesity, especially given that not all obese individuals possess the associated metabolic derangements that place them at greater CVD risk. A systematic examination of the effects of ovarian aging on obesity metabolism in relation to CVD risk markers is needed to better distinguish between those who will likely suffer obesity-associated cardiovascular complications and those who will not. [unreadable] [unreadable] [unreadable]